tbuckley/cabot-search huggingface dataset:
CTNI-13. A FIRST-IN-HUMAN PHASE 0/1 TRIAL OF 5-AMINOLEVULINIC ACID SONODYNAMIC THERAPY (5-ALA SDT) IN RECURRENT GLIOBLASTOMA
Authors: Nader Sanai, An-Chi Tien, Artak Tovmasyan, Yu-Wei Chang, Tigran Margaryan, Kristen Hendrickson, Jennifer Eschbacher, Wonsuk Yoo, Jocelyn Harmon, Amy Hong, Christopher Quarles, Igor Barani, Lea Alhilali, Zaman Mirzadeh, Shwetal Mehta
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND 5-ALA SDT is not a blood-brain barrier disruption technique, but rather a first-in-class drug-device therapy exploiting the heme synthesis pathway in recurrent glioblastoma (rGBM). Following IV 5-ALA administration, aberrant tumor metabolism results in protoporphyrin-IX (PpIX) accumulation. Activation of PpIX by non-invasive, non-ablative magnetic resonance-guided focused ultrasound (MRgFUS) induces reactive oxygen species and tumor cell death. This first-in-human Phase 0/1 study investigates the feasibility, safety, and biological effects of 5-ALA SDT in rGBM patients. METHODS Six hours prior to SDT, adult patients with rGBM were administered 10mg/kg of an IV formulation of 5-ALA (SONALA-001). Patients were assigned to one of three ascending acoustic energy levels of MRgFUS (200J/400J/800J, measured at transducer surface), followed by a four-day interval prior to planned tumor resection. In each patient, 50% of the enhancing and nonenhancing tumor volume was targeted with MRgFUS with the untreated tumor serving as an internal control. The Optimal Biological Dose (OBD) associated with 5-ALA SDT is the energy level associated with greatest tumor cell death. RESULTS 8 patients were accrued across all energy levels, and none demonstrated drug- or device-related adverse events. Compared to internal control tissue, the apoptosis biomarker, cleaved caspase-3, was elevated in all patients, but most prominently at the 200J energy level. The oxidative stress biomarkers 4-hydroxynonenal, glutathione, cysteine, and thiol were elevated in treated vs. control tissues at all energy levels. The mean Cmax for 5-ALA and PpIX in plasma were 305 µM and 65 nM, respectively. No off-target histological or radiographic alterations were detected in any patient. CONCLUSIONS This first-in-human Phase 0/1 study of a new therapeutic modality for rGBM patients demonstrates that 5-ALA SDT is safe at 200 to 800J and likely induces targeted cell death in rGBM patients via oxidative stress. At 10mg/kg of 5-ALA, the OBD is at or lower than 200J.
CSIG-39. PROSTAGLANDIN-SCULPTING; REPRODUCTIVE DRIVERS OF THE GBM TUMOR IMMUNE LANDSCAPE
Authors: Martyn Sharpe, Alexandra Baskin, David Baskin
Journal: Neuro-Oncology (2022)

Abstract Introduction We have reported that GBM utilize sex-steroids and reproduction-specific proteins to hijack the granting of immune-privilege to male/partner-specific antigens/epitopes. We have extended upon this foundation to examine other examples of immunosuppressive tissue-mimicry mechanisms that GBM deploy. The generation of prostaglandins D2, E2 and F2 and reproductive proteins are used by GBM tumors to activate discrete immune-cell types and to drive vascularization and growth. METHODS Three GBM-transcriptome databases were mined and analyzed utilizing pathway, stratification, correlation and survival analysis. RESULTS PGD2 and PGF2 synthesis is driven by C3AR1 microglial signaling, in response to complement C3a activation by GBM expression of C3 and CFB. PGD2 is expressed in hypoxic tumors and PGF2 is expressed in normoxic ones. PGF2 drives the hematopoietic stem cell angiogenic pathway, via TPBG/CXCL12/CXCR4. This is the primary pathway promoting early placental vascularization and vascular development/repair of mucosal tissues. Microglial synthesized PGD2 drives the CCL5/CCR5 axis, a pathway central to cyclic vascularization of uterine tissues and in wound healing, via VEGFA. Generation of CCL5 also recruits CCR5-positive monocytes, which are then driven into M2-TAM phenotype. CCL5 also recruits and drive myeloid cells into MDSCs. SOX9 drives masculinization of embryonic gonads. GBM expression of SOX9 correlates with seminal heat shock protein expression. These reproductive HSPs are associated with neutrophil generation of PGE2 in GBM tumors, mirroring their role in the semenized female reproductive tract, where they support PGE2 synthesis and aid EGFR driven vascularization CONCLUSIONS The ability of GBM to modulate the anti-tumor response is central to their lethality. The discrete, cell-specific mechanisms revealed will allow personalized medicine using off-the-shelf drug therapy.
NIMG-44. DSC-MRI FRACTIONAL TUMOR BURDEN VOLUME PREDICTS OVERALL SURVIVAL IN UNMETHYLATED NEWLY DIAGNOSED HIGH GRADE GLIOMA
Authors: Stephanie Armstrong, Melissa Prah, Jennifer Connelly, Max Krucoff, Wade Mueller, Kathleen Schmainda
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE Image maps of Fractional Tumor Burden (FTB), derived from dynamic susceptibility contrast (DSC) perfusion MRI, provide clinically meaningful information for glioma treatment management. The goal of this study was to determine if presurgical FTB is predictive of overall survival (OS) in high-grade glioma (HGG) classified according to WHO 2016 criteria. METHODS Standardized relative cerebral blood volume (sRCBV) maps were created and co-registered with T1+C images using Horos (Version 4.0.0) and Imaging Biometrics software (Version 21.05) (Elm Grove, WI). Enhancing tumor volumes were determined from calibrated pre/post T1 difference (dT1) maps. Tissue-validated sRCBV thresholds were used to create FTB class maps within enhancing lesion with red regions (sRCBV &amp;gt; 1.556) indicating a high probability of vascular tumor, blue regions (sRCBV&amp;lt; 1.0) indicating avascular (non-tumor) tissue and yellow representing tissue with a lower probability of vascular tumor. FTB volume fractions (FTBv) for all vascular tumor (sRCBV &amp;gt;1.0) or the most vascular tumor (sRCBV &amp;gt; 1.566) were determined. Subjects were separated by MGMT methylation status. GraphPad Prism statistical software (Version 9.3.1) was used for Kaplan Meier survival analysis at 12 and 24 months with patients stratified by median FTBv. RESULTS Forty-one subjects (23 males, 18 females) with a median age of 59.45 years were included. Median 12-month and overall survival of unmethylated groups stratified by FTBv (rCBV &amp;gt; 1.0) of 8.33cc was 10.69 and 15.35 months (p=.0453; p=.0317). Unmethylated subjects stratified with FTBv (rCBV &amp;gt; 1.566) of 7.13cc had a median survival of 10.69 and 15.20 with short- and long-term survival distinguished at 12 months (p=0.0033), 24 months (p=0.0002) and overall (p=0.0002). No significant difference in survival was found between the methylated subgroups with FTBv (rCBV &amp;gt; 1.0) or FTBv (rCBV &amp;gt; 1.566) stratified analyses. CONCLUSION These results demonstrate that pre-surgical FTBv is predictive of OS in newly diagnosed unmethylated high-grade glioma.
RADT-05. VOLUMETRIC MODULATED ARC THERAPY CRANIOSPINAL IRRADIATION UTILIZING A VERTEBRAL BODY SPARING APPROACH: A DOSIMETRIC ANALYSIS
Authors: Jennifer Matsui, Haley Perlow, Ashlee Ewing, Catherine Cadieux, Dukagjin Blakaj, Sasha Beyer, Evan Thomas, Raju Raval, Joshua Palmer
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral-body-sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. We hypothesize that VBS-CSI utilizing volumetric modulated arc therapy (VMAT) will effectively reduce vertebral body dose while minimizing dose to surrounding organs-at-risk (OAR) for adult patients with LMD. METHODS Ten adult patients with LMD received CSI, 30 Gy in 10 fractions. These patients were initially treated with a variety of VMAT and IMRT treatment techniques. These patients were then retrospectively replanned using VMAT VBS-CSI. For their VBS-CSI replan, full VMAT arcs for the brain fields matched to two spine isocenters for the upper and lower spine were created utilizing limited posterior arcs. The PTV was created with margins of 3mm uniformly around the brain contour and 7mm around the spinal canal. To further decrease the vertebral body dose, an avoid entry and exit contour was created. This structure was a margin on the PTV anteriorly designed to carve dose out of the vertebral bodies while still maintaining coverage to the PTV. RESULTS All 10 patients had a reduction in vertebral body dose with VMAT VBS-CSI when compared to their initial plan. The mean vertebral dose for the VBS-CSI plans had an average reduction of 33% compared to the initial plans. The mean dose to the small bowel and esophagus were reduced by 46% and 67%, respectively. CONCLUSIONS VBS-CSI may be utilized to minimize dose to surrounding OARs and vertebral bodies. In this study, VMAT VBS-CSI led to significant reductions in vertebral body dose while also minimizing dose to other OARs. VMAT VBS-CSI may be an acceptable alternative to proton-based VBS-CSI in an adult population with LMD. Prospective evaluation is warranted.
TMET-04. DETECTING DYNAMIC PYRUVATE TUMOR METABOLISM IN PATIENTS WITH GLIOMA USING HYPERPOLARIZED CARBON-13 METABOLIC IMAGING
Authors: Yan Li, Janine Lupo, Adam Autry, Sana Vaziri, Jeremy Gordon, Marisa Lafontaine, Chen Hsin-Yu, Yaewon Kim, Jasmine Hu, Wendy Ma, Javier Villanueva-Meyer, Peder Larson, Duan Xu, Nancy Ann Oberheim Bush, Jennifer Clarke, Daniel Vigneron, Susan M Chang
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Hyperpolarized carbon-13 (HP-13C) MR enables rapid dynamic imaging of metabolic pathways in the human brain using non-toxic, non-radioactive metabolites as tracers. This study presents our unique experience on the benefit of using [1-13C]pyruvate and [2-13C]pyruvate MR for evaluating patients with glioma. METHODS 132 scans (71 using an integrated 13C /1H coil) including steady-state 1H-MRSI (~10 min) and dynamic HP-13C imaging (60 sec) following injection of HP [1-13C]pyruvate (N=125) or [2-13C]pyruvate (N=7) were acquired from 46 patients with glioma (18F/28M; 15 IDH-mutant, 27 IDH-wildtype, 4 IDH-status-unknown). Maps of temporally-summed 13C-metabolite signals, ratios, and kinetic rate constants were calculated for contrast-enhancing, nonenhancing, and normal-appearing-white-matter (NAWM) regions and compared to steady-state metabolic metrics. RESULTS The only adverse event, in a single patient, was a burning sensation after the injection that resolved after saline flush. The mean time-to-injection of HP probes was 58.6±14.0 sec. Signal-to-noise ratios of [1-13C]lactate and [13C]bicarbonate within the NAWM from the HP [1-13C]pyruvate data were 53±39 and 13±6, respectively. The SD/mean of repeated injections (N=3) for lactate/pyruvate and pyruvate-to-lactate conversion rates were 3.8±3.1% and 6.5±3.1% in the NAWM, respectively. Patients with progressive GBM had significantly higher lactate/pyruvate and lower bicarbonate/lactate (p&amp;lt; 0.05) in contrast- and non-enhancing lesions compared to NAWM. Significantly elevated lactate/pyruvate and reduced bicarbonate/lactate (p&amp;lt; 0.01) were found in contrast-enhancing compared to nonenhancing regions, whereas choline/NAA and steady-state 1H-lactate levels were similar. HP [2-13C]pyruvate data showed reduced glutamate/pyruvate and pyruvate-to-glutamate conversion rates in T2 lesions compared to contralateral normal-appearing brain in IDH-mutant gliomas, consistent with known metabolic reprogramming. CONCLUSION This study demonstrates the potential benefit of dynamic HP-13C MRI for evaluating patients with glioma, which provides unique and spatially distinct contrast compared to steady-state metabolic imaging. Ongoing studies will further characterize dynamic metabolism in specific glioma subtypes and provide biomarkers for evaluating responses to treatment.
DISP-02. CENTRAL NERVOUS SYSTEM METASTASES FROM EXOCRINE GLANDS CARCINOMA: CASE MANAGEMENT IN LOW RESOURCE SETTING AND REVIEW OF LITERATURE
Authors: Jared Paul Golidtum, Joseph Erroll Navarro, Kenny Seng, Jose Carlos Alcazaren, Kevin Paul Ferraris
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Head and neck exocrine gland tumors metastases to central nervous system (CNS) account for less than 1% with median survival of less than 6 months. Unlike brain metastases from lung, breast, melanoma, and colon, there is no established consensus or published clinical guidelines in the management from excorine glands. Filipino patients are manage individually but experienced delays due to limited access to a tertiary level health care and with scarcity of treatment protocols. Methods and RESULTS We present two cases with exocrine glands carcinoma with CNS metastases. First case is a 51/F with a known case of left parotid cystic adenocarcinoma s/p parotidectomy and radiation therapy 2 years prior to the development of neurological deficits and COVID-19 infection, neuroimaging noted extra-axial 7.5 x 5 x 4.5 cm contrast enhancing tumor at bilateral frontal convexity. She underwent bifrontal craniotomy, gross total excision of tumor and anterior sagittal sinus, histopathology results cystic adenocarcinoma. She was discharged GOS 2, planned for chemoradiotherapy but lost to follow up and expired after 2 months post op. Second case is a 28/M known case of lacrimal gland pleomorphic adenocarcinoma OD s/p excision biopsy 2 years prior to the development of multiple right frontal lobe, right orbital wall and right pterion metastases. He underwent gross excision of extracranial and intracranial tumors and a right orbital exenteration. He was discharged GOS 2 and underwent chemoradiation as outpatient with good tumor control and no tumor recurrence after 1 year of treatment. DISCUSSION CNS metastases from exocrine glands are rare and difficult to manage since no approved protocol was established. Patients in low resource setting were then manage on individual basis since molecular and genomic studies are not available. The delays in the management are multifactorial such as geographic disadvantages, COVID-19 pandemic, and government's inadequate support for health system.
QOL-03. CLINICAL CHARACTERISTICS AND FACTORS ASSOCIATED WITH SEIZURES IN GLIOMA PATIENTS AT THE NATIONAL CANCER CENTER DHARMAIS HOSPITAL IN JAKARTA, INDONESIA
Authors: Nathasia Suryawijaya, Rini Andriani, Siswanto Agus Wilopo
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Seizures are a common presentation of gliomas that substantially impact morbidity and quality of life. Little is known about the prevalence of seizures among glioma patients in Indonesia. Furthermore, there is no publication regarding clinical characteristics related to this prevalence. OBJECTIVE To measure the prevalence of seizures among glioma patients and its association with tumor grade (low or high), type, and location. METHODS This is a retrospective study based on the medical records of all patients diagnosed with glioma according to histopathology findings. There were 65 patients admitted to the National Cancer Center Dharmais Hospital, Jakarta between January 2019 and December 2020. The demographic characteristics and clinical data were extracted, including clinical and tumor characteristics. Using logistic regression, an odds ratio (OR) with 95% confidence intervals was used to investigate the association between factors related to seizures. RESULTS A total of 65 patients (39 males and 26 females) were included in the study. Most of the patients are ranging from 40 to 49 years old (39%). The prevalence of seizures is relatively high which is 42 out of 65 patients (64.6%). Headache (95%) is the most common complaint in patients. Our study shows that grading and location of tumor were significantly associated with seizure in glioma patients among clinical manifestations (headache, neurological deficits) and pathological classification (p=0.005 and p=0.022). Bivariate analysis using logistic regression showed that low-grade glioma had a 12.2-fold increase in the risk of developing seizures compared to high-grade gliomas with a 95% CI of 1.50 to 99.9 (P&amp;lt; 0.05). Moreover, the temporal location of the tumor had a 5.6-fold increase in the risk of developing seizures compared to the parietal location with a 95% CI of 1.01 to 30.9. CONCLUSIONS Grading and location of the tumor were factors associated with seizures in glioma patients.
DDEL-14. SYSTEMIC THERAPY USE FOR THE TREATMENT OF MENINGIOMA: A SYSTEMATIC REVIEW
Authors: Khalid Taleb, Anna Laucis
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION Meningiomas are the most common primary central nervous system tumor. Many studies have investigated systemic therapy agents for treating meningiomas, but no study has systematically evaluated the various agents used while comparing outcomes. The goal of this study was to investigate the recent systemic therapy agents used to treat meningioma tumors and to compare relevant clinical outcomes such as progression-free survival and overall survival in patients with meningioma tumors receiving systemic therapy agents as part of their care.Materials and METHODS A systematic literature review was performed to investigate systemic therapy agents used to treat meningioma tumors. The PubMed database was used for this review and articles published from 7/4/2011 to 7/4/2021 were evaluated. The exclusion criteria included the following: animal and cell line studies, case reports, review articles, articles in a foreign language (other than English), as well as articles not related to meningioma or to systemic therapy agents. RESULTS 163 articles were initially evaluated. After excluding 152 articles using the exclusion criteria for our study, a total of 11 articles exploring 14 different systemic therapy agents were ultimately included and compared, mainly focusing on the two clinical outcomes of progression-free survival and overall survival. The study findings suggest that Bevacizumab may have the most promising results for reducing peri-tumoral edema and extending progression-free survival, with the highest observed progression-free survival at six months of 86% compared to lower progression-free survival for other systemic therapy agents. CONCLUSION This systematic review study evaluated systemic therapy agents used to treat meningioma tumors. Bevacizumab was found to have the most promising results overall. However, further studies are now needed to evaluate the efficacy and possible side effects of Bevacizumab amongst a larger population of patients with different meningioma tumor grades, locations, and treatment responses.
QLTI-03. AN INNOVATIVE APPROACH TO ACCESSIBLE INFORMATION FOR BRAIN TUMOUR PATIENTS AND THEIR LOVED ONES
Authors: Victoria Hurwitz, Jessica La, Sarah Hedges, Charlotte Robinson, Ellie Kostick, Aeron Suarez, Jose Lavrador, Ranjeev Bhangoo, Lucy Brazil
Journal: Neuro-Oncology (2022)

Abstract Patient information for cancer patients is acknowledged for its vital contribution to informed consent and a positive patient experience. It forms a measure to which UK oncology centres are held to account in the national cancer patient experience survey. It could be argued that this has driven the production of such information rather than it being designed to best meet the need of the neuro-oncology patient. With this in mind a YouTube channel was set up after consulting current High Grade Glioma patients on their preferred medium. Patients wanted short clips in a conversational style explaining aspects of their treatment and the pathway. They wanted it to be available in a medium that they were familiar with either s a podcast or YouTube shorts. The CNS team requested patients choose the name of the channel and began making short videos with patients and professionals on subjects suggested by patients. In twelve weeks, we have produced 23 videos, which have had 2282 views and 105 hours of watch time. The average person watches for two hours and forty-six minutes. It is possible to extrapolate from this that people are engaging with the content. The availability of information in this form has reduced the length of conversations and emails with the CNS’s pre-operatively. Patients have reported a greater sense of comfort from hearing other patient’s stories. The authors acknowledge there is not enough data available yet to formerly support this. In conclusion patient information should be designed to meet the needs of the patient not the guidance. It needs to be accessible to patients who have neurological impairments including changes in vision and concentration and provided in a medium that is current, visual and easily accessible.
BIOM-62. INTEGRATED GENOMIC PROﬁLING OF LONG-TERM GLIOBLASTOMA SURVIVORS
Authors: PengFei Xu, ZhongPing Chen
Journal: Neuro-Oncology (2022)

Abstract Glioblastoma (GBM) is a fatal brain tumor, and few patients survive beyond 5 years. Therefore, a study of genomic alterations in GBM long-term survivors is essential for insights into tumor biology and biomarker identiﬁcation. In our study, 13 GBM long-term survivors (overall survival &amp;gt;60 months) and 19 short-term survivors (overall survival &amp;lt; 24 months) were retrospectively collected, and surgically resected tumor tissues and normal blood controls were extracted and were performed whole exome sequencing and transcriptome sequencing. Our results revealed that although no significant differences were found in the composition of driver genes between the two groups, mutation signature analysis of two GBM groups revealed that the proportion of mutation signature 19 was higher in the longer survivors than in the shorter survivors (P=0.059). Analysis of copy number variants showed that the longer survivors group had higher copy number variants at the chromosomal level (P=0.049). At the chromosome Arm level, the proportion of 19p amplification and 19q amplification in the longer survivors group was significantly higher than in the short survival group (P=0.001/0.002). And in the TCGA GBM dataset, GBM patients with 19p amplification also had a better prognosis (log-rank P=0.04). In conclusion, the proportion of mutation signature 19 and amplification of 19p was potential prognostic molecular features for GBM.